The impact of salpingectomy and single dose systemic methotrexate treatments on ovarian reserve in ectopic pregnancy Cagdas Sahin M.D.a, Enes Taylan M.D.a, Ali Akdemir M.D.a, Banu Ozgurelb, Dilek Taskıran M.D.c, Ahmet M. Ergenoglu M.D.a   aEge University School of Medicine, Department of Obstetrics and Gynecology, Bornova, Izmir, Turkey. bYasar University School of Science and Letter, Department of Actuarial, Bornova, Izmir, Turkey. cEge University School of Medicine, Department of Physiology, Bornova, Izmir, Turkey.

Ectopic Pregnancy Ectopic pregnancy; maternal mortality and morbidity. Complicates 1-2 % of all pregnancies Various localizations out of the uterine cavity fallopian tubes - most common place Current treatment medical (Methotrexate) (single – multi dose) surgical (salpingectomy, salpingostomy or milking)

Treatment and Ovarian Reserve Methotrexate (MTX), chemotherapeutic agent - folic acid antagonist targeting actively proliferating cells concern of adverse effect on fertility Salpingectomy, diminishing ovarian blood supply

Anti-Müllerian hormone glycoprotein, preantral and small antral follicles relatively constant little impact of outer determinants correlated with number of oocytes retrieved, quality of embryos and clinical pregnancy and live birth rates The aim of this study was to investigate the effects of salpingectomy and methotrexate treatment on ovarian reserve in ectopic pregnancy by measuring AMH levels.

Material and Methods A total of 131 patients with EP MTX (50 mg/m2) single dose of systemic -hCG levels were measured on the 4th and 7th days More than 15% reduce in levels History of ; ovarian surgery, endometriosis, systemic chemotherapy, ART Clinically stable -hCG levels  10.000 IU/ml, Without visible fetal cardiac activity on ultrasound Adnexal fetal mass < 4 cm in size selected for systemic single dose of MTX treatment.     history of ovarian surgery, endometriosis and systemic chemotherapy that could have potential negative effect on ovarian reserve were excluded. History of infertility and assisted reproduction technology (ART) treatments were also exclusion criteria because of possible unknown ovarian pathologies and altered ovarian physiology, respectively

Group 1 (single dose MTX only) (n:55) Group 2 (Salpingectomy only) (n:61) Group 3 (Salpingectomy following MTX)(n:15) Demographic data AMH plasma levels Pretreatment Posttreatment 1st month Postreatment 3th month The quantitative data were tested for normality using the Kolmogorov Smirnov test. Normally distributed variables were compared using one-way ANOVA followed by the Bonferroni post hoc test to assess differences. Non-normally distributed variables were compared using the Kruskal-Wallis. SPSS statistical software, version 11 was used for statistical analysis. A P value of  0.05 was considered as statistical significant.

Results Çalışmaya 131 hasta dahil edilmiştir. Hasta yaşı, BMI, sigara iiçimi, gravide, parite, tedavi öncesi ve tedavi sonrası (1 ve 3 ay) AMH seviyeleri tablo 1-2 de gösterilmiştir. Demografik açıdan gruplar arsı fark yoktur.

Results Tedavi öncesi AMH değerleri açısından 3 grup arası fark saptanmamıştır (p:0.213). tedavi sonrası 1 aydaki AMH değerleri açısında grup 1 ve 2 arasında (p:0.043) ve grup 1 ve grup 3 arasında (p:0.035) anlamlı farklılık saptanmıştır. Fakat bu farklılıkların 3 ay daki AMH değerledi karşılaştırıldığında ortadan kalktığı saptanmıştır. Aynı zamanda aynı grup içinde AMH değerlerleri kendi içerisinde karşılaştırılmıştır. Sonucunda sadece grup 3 te tedavi sonrası 1 ay ve tedavi öncesi AMH değerleri arasında farklılık saptanmıştır (0.03). Fakat daha önceki sonuçlarda olduğu gibi bu farklılığında tedavi sonrası 3 ay da bu farklılığın kaybolduğu görülmüştür.

Discussion EP life-threatening condition Medical and surgical treatment and ovarian reserve ???? Uyar et al (Fertil Steril 2013) no significant effect of MTX on ovarian reserve. Boots et al (Fertil Steril 2013) MTX does not compromise ovarian reserve. Hill et al (Fertil Steril 2014), number of doses of MTX is not correlated with in change of FSH, AFC. Uyar et al. reported that there was no significant effect of single dose MTX treatment on ovarian reserve (6). Also Boots et al. investigated the effect of single dose MTX administration for EP after in vitro fertilization (IVF) on ovarian reserve and concluded as; it does not compromise ovarian reserve, responsiveness or subsequent IVF success (7). Similar results were reported in a large cohort study by Hill et al (8). They enounced that the number of doses of MTX treatment was not correlated with the change in values of FSH, AFC and oocyte yield.

Discussion Ulug et al (EJObstet Gynecol Reprod Biol 2014), MTX and salpingectomy decreases the ovarian reserve. Ye et al (Am J Obstet Gynecol 2015), salpingectomy has a negative effect. Lin et al (JMIG 2013), salpingectomy has no effect on ovarian reserve. Almog et al (Fertil Steril 2011), salpingectomy does not influence ovarian reserve. However, Ulug et al proposed vice versa in their study. They stated that single or multiple doses of MTX and salpingectomy decreases the ovarian reserve markers including AMH and follicle counts (9). In a recent article by Ye et al. the effect of salpingectomy on ovarian reserve was retrospectively evaluated in a study group of 198 patients who underwent unilateral or bilateral salpingectomy before IVF treatment. They proposed that salpingectomy has a negative effect on ovarian reserve (5). On the contrary, Lin et al. proposed that salpingectomy has no effect on ovarian reserve (10). In addition to this, Almog et al. asserted that salpingectomy does not influence ovarian response in controlled ovarian hyperstimulation for IVF treatment (15).

Conclusion As a conclusion, based on the results of majority of researches and our present study, current applications of single dose systemic MTX treatment and laparoscopic unilateral salpingectomy are safe treatment options for EP with no obvious harmful effect on ovarian reserve.